The mammalian brain is a highly oxidative organ and requires a constant supply of oxygen. We are investigating the relationships between oxygen tension and tissue energetics in brain. Cortical oxygen tensions are measured in anesthetized rats during a graded hypoxia protocol using EPR oximetry. In parallel experiments, we measure brain energetics using phosphorus NMR. With the latter technique, we can quantify ATP, PCR, PI and intracellular pH. The free ADP concentration can also be quantified. The oxygen tension at which the brain cannot maintain "resting" metabolic homeostasis is determined by that which causes a purturbation in either high energy phosphates or pH. It is recognized that the results will be very sensitive to experimental conditions. The long term goal is to use the protocol to investigate metabolic protectents and to determine if these "protectants" will reduce the critical pO2 (thereby increasing the brain's tolerance of hypoxia).